title: Delayed response in the rat frontal lobe transcriptome to perinatal exposure to the flame retardant BDE-47.
abstract: BDE-47 is the most prevalent congener of polybrominated diphenyl ethers, which are widely used flame retardants, and is known for endocrine and behavioral disrupting properties in animals. Transient effect on spontaneous motor activity in rats following perinatal exposure to BDE-47 at low doses, relevant to human exposure, was reported in our previous study. The objective of this study was to screen for the long-term effects on gene expression in the brain of rats perinatally exposed to BDE-47. Wistar dams were exposed to BDE-47 (0.002 and 0.2 mg kg(-1) body weight) from gestation day 15 to postnatal day (PND) 20. Total RNA was extracted from the whole brain at PND10 and the brain frontal lobes at PND41 and hybridized to whole-genome RNA expression microarrays. The genes, differentially expressed 1.5-fold, were analyzed with the DAVID bioinformatics resources for cluster and gene-term enrichment. At PND41, clusters of genes involved in nerve impulse transmission, nervous system development and functioning, and core biosynthetic process were altered, including several downregulated genes of cation channels. Representation of LINE1 RNA was decreased significantly. Altered expression of genes involved in neurodevelopment occured at least 3 weeks after the last exposure and the behavioral manifestation of low dose BDE-47 toxicity.
authors.affiliation: Département Obstétrique Gynécologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, Québec, Canada, J1H 5N4.
authors.forename: Alexander
authors.initials: A
authors.lastname: Suvorov
authors.forename: Larissa
authors.initials: L
authors.lastname: Takser
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D055106:Genome-Wide Association Study; D055768:Halogenated Diphenyl Ethers; D018811:Maternal Exposure; D055495:Neurogenesis / Q000187:drug effects* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether